Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome

Abstract

The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G 2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G 2 checkpoint in yeast.

Keywords

Li–Fraumeni syndromeBiologyGeneticsGeneCancer researchMutationTumor suppressor geneDNA damageGermlineCancerKinaseGermline mutationDNACarcinogenesis

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Publication Info

Year: 1999
Type: article
Volume: 286
Issue: 5449
Pages: 2528-2531
Citations: 897
Access: Closed

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APA Style

                            
                                
                                    Daphne W. Bell, 
                                
                                    Jennifer M. Varley, 
                                
                                    Tara E. Szydlo
                                
                                et al.
                            
                            (1999). 
                            Heterozygous Germ Line <i>hCHK2</i> Mutations in Li-Fraumeni Syndrome. 
                            Science
                            , 286
                            (5449)
                            , 2528-2531.
                            https://doi.org/10.1126/science.286.5449.2528
                        

Identifiers

DOI: 10.1126/science.286.5449.2528

Heterozygous Germ Line <i>hCHK2</i> Mutations in Li-Fraumeni Syndrome